Curam/Curam Solutab

Co-amoxiclav: Amoxicillin and clavulanic acid.

Curam 375 mg film-coated tablets: Each tablet contains: 250 mg amoxicillin (as amoxicillin trihydrate) and 125 mg clavulanic acid (as potassium clavulanate).
Curam 625 mg film-coated tablets: Each tablet contains: 500 mg amoxicillin (as amoxicillin trihydrate) and 125 mg clavulanic acid (as potassium clavulanate).
Curam 1000 mg film-coated tablets: Each tablet contains: 875 mg amoxicillin (as amoxicillin trihydrate) and 125 mg clavulanic acid (as potassium clavulanate).
Curam 156.25 mg/5 ml powder for oral suspension: Each 5 ml [1 measuring-spoonful] of the reconstituted suspension contains: 125 mg amoxicillin (as amoxicillin trihydrate) and 31.25 mg clavulanic acid (as potassium clavulanate).
Curam forte 312.5 mg/5 ml powder for oral suspension: Each 5 ml [1 measuring-spoonful] of the reconstituted suspension contains: 250 mg amoxicillin (as amoxicillin trihydrate) and 62.5 mg clavulanic acid (as potassium clavulanate).
Curam 457 mg/5 ml powder for oral suspension: Each 5 ml [1 measuring-spoonful] of the reconstituted suspension contains: 400 mg amoxicillin (as amoxicillin trihydrate) and 57 mg clavulanic acid (as potassium clavulanate).
Curam Solutab 1000 mg Dispersible Tablets: Each tablet contains 875 mg of amoxicillin in the form of amoxicillin trihydrate and 125 mg clavulanic acid in the form of clavulanate potassium.
Excipients/Inactive Ingredients: Curam 375 mg and 625 mg film coated tablets: Magnesium stearate, Polyvidone, Talc, Croscarmellose Sodium, Microcrystalline Cellulose, Triethyl Citrate, Ethyl Cellulose, Hypromellose, Titanium dioxide.
Curam 1000 mg film coated tablets: Magnesium stearate, Polyvidone, Talc, Croscarmellose Sodium, Microcrystalline Cellulose, Triethyl Citrate, Ethyl Cellulose, Hypromellose, Titanium dioxide, Silicon dioxide.
Curam 156.25 mg/5 ml powder for oral suspension and Curam forte 312.5 mg/5 ml powder for oral suspension: Lemon flavouring powdered, Peach Apricot flavouring powdered, Orange flavouring powdered, Anhydrous citric acid, Anhydrous Trisodium Citrate, Aspartame, Talc, Guar Gum, Silicon dioxide precipitated.
Curam 457 mg/5 mL powder for oral suspension: anhydrous citric acid, sodium citrate, microcrystalline cellulose, carmellose sodium, xanthan gum, colloidal anhydrous silica, silicon dioxide, aroma strawberry, saccharin sodium, mannitol.
Curam Solutab 1000 mg Dispersible Tablets: Tropical blend flavor, Sweet orange flavor, Aspartame E951, Colloidal anhydrous Silica, Ferric oxide (yellow) E172, Talc, Hydrogenated castor oil, Silicified microcrystalline cellulose (mixture of microcrystalline cellulose 98% and colloidal anhydrous silica 2%).

Pharmacotherapeutic group: Combinations of penicillins, incl. beta-lactamase inhibitors. ATC code: J01CR02.
PHARMACOLOGY: Pharmacodynamics: Mode of action: Amoxicillin is a semi-synthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins, PBPs) in the biosynthetic pathway of bacterial peptidoglycan, which is an integral structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, which is usually followed by cell lysis and death.
Amoxicillin is susceptible to degradation by beta-lactamases produced by resistant bacteria and therefore the spectrum of activity of amoxicillin alone does not include organisms which produce these enzymes.
Clavulanic acid is a beta-lactam structurally related to penicillins. It inactivates some beta-lactamase enzymes thereby preventing inactivation of amoxicillin. Clavulanic acid alone does not exert a clinically useful antibacterial effect.
PK/PD relationship: The time above the minimum inhibitory concentration (T>MIC) is considered to be the major determinant of efficacy for amoxicillin.
Mechanisms of resistance: The two main mechanisms of resistance to amoxicillin/clavulanic acid are: Inactivation by those bacterial beta-lactamases that are not themselves inhibited by clavulanic acid, including class B, C and D.
Alteration of PBPs, which reduce the affinity of the antibacterial agent for the target.
Impermeability of bacteria or efflux pump mechanisms may cause or contribute to bacterial resistance, particularly in Gram-negative bacteria.
Breakpoints: MIC breakpoints for amoxicillin/clavulanic acid are those of the European Committee on Antimicrobial Susceptibility Testing (EUCAST). (See Table 1.)

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The prevalence of resistance may vary geographically and with time for selected species, and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.
The prevalence of resistance to amoxicillin/clavulanic acid in United Kingdom is listed as table as follows. (See Table 2.)

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Pharmacokinetics: Absorption: Amoxicillin and clavulanic acid are fully dissociated in aqueous solution at physiological pH. Both components are rapidly and well absorbed by the oral route of administration.
Absorption of amoxicillin/clavulanic acid is optimised when taken at the start of a meal. Following oral administration, amoxicillin and clavulanic acid are approximately 70% bioavailable. The plasma profiles of both components are similar and the time to peak plasma concentration (T_max) in each case is approximately one hour.
The pharmacokinetic results for a study, in which amoxicillin/clavulanic acid (250 mg/125 mg tablets three times daily) was administered in the fasting state to groups of healthy volunteers are presented as follows. (See Table 3.)

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Amoxicillin and clavulanic acid serum concentrations achieved with amoxicillin/clavulanic acid are similar to those produced by the oral administration of equivalent doses of amoxicillin or clavulanic acid alone.
Distribution: About 25% of total plasma clavulanic acid and 18% of total plasma amoxicillin is bound to protein. The apparent volume of distribution is around 0.3-0.4 l/kg for amoxicillin and around 0.2 l/kg for clavulanic acid.
Following intravenous administration, both amoxicillin and clavulanic acid have been found in gall bladder, abdominal tissue, skin, fat, muscle tissues, synovial and peritoneal fluids, bile and pus. Amoxicillin does not adequately distribute into the cerebrospinal fluid.
From animal studies there is no evidence for significant tissue retention of drug-derived material for either component. Amoxicillin, like most penicillins, can be detected in breast milk. Trace quantities of clavulanic acid can also be detected in breast milk (see Use in Pregnancy & Lactation). Both amoxicillin and clavulanic acid have been shown to cross the placental barrier (see Use in Pregnancy & Lactation).
Biotransformation: Amoxicillin is partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to up to 10 to 25% of the initial dose. Clavulanic acid is extensively metabolized in man and eliminated in urine and faeces and as carbon dioxide in expired air.
Elimination: The major route of elimination for amoxicillin is via the kidney, whereas for clavulanic acid it is by both renal and non-renal mechanisms.
Amoxicillin/clavulanic acid has a mean elimination half-life of approximately one hour and a mean total clearance of approximately 25 l/h in healthy subjects. Approximately 60 to 70% of the amoxicillin and approximately 40 to 65% of the clavulanic acid are excreted unchanged in urine during the first 6 h after administration of single Amoxicillin/clavulanic acid 250 mg/125 mg or 500 mg/125 mg tablets. Various studies have found the urinary excretion to be 50-85% for amoxicillin and between 27-60% for clavulanic acid over a 24 hour period. In the case of clavulanic acid, the largest amount of drug is excreted during the first 2 hours after administration.
Concomitant use of probenecid delays amoxicillin excretion but does not delay renal excretion of clavulanic acid (see Interactions).
Age: The elimination half-life of amoxicillin is similar for children aged around 3 months to 2 years and older children and adults. For very young children (including preterm newborns) in the first week of life the interval of administration should not exceed twice daily administration due to immaturity of the renal pathway of elimination. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Gender: Following oral administration of amoxicillin/clavulanic acid to healthy male and female subjects, gender has no significant impact on the pharmacokinetics of either amoxicillin or clavulanic acid.
Renal impairment: The total serum clearance of amoxicillin/clavulanic acid decreases proportionately with decreasing renal function. The reduction in drug clearance is more pronounced for amoxicillin than for clavulanic acid, as a higher proportion of amoxicillin is excreted via the renal route. Doses in renal impairment must therefore prevent undue accumulation of amoxicillin while maintaining adequate levels of clavulanic acid (see Dosage & Administration).
Hepatic impairment: Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals.
Toxicology: Preclinical safety data: Curam FC tab/oral susp and Curam 457 mg/5 mL oral susp: Nonclinical data reveal no special hazard for humans based on studies of safety pharmacology, genotoxicity and toxicity to reproduction.
Repeat dose toxicity studies performed in dogs with amoxicillin/clavulanic acid demonstrate gastric irritancy and vomiting, and discoloured tongue.
Carcinogenicity studies have not been conducted with amoxicillin/clavulanic acid or its components.
Curam Solutab: a) Acute toxicity: Investigations of the acute toxicity (LD50) of amoxicillin and clavulanic acid in adult animals and neonates have confirmed very low toxicity potential. The LD50 of clavulanic acid (potassium salt) is determined by the potassium content. Administration of clavulanic acid (potassium salt) together with amoxicillin does not result in any unexpected or synergistic toxicity.
b) Chronic toxicity/subchronic toxicity: Not relevant.
c) Mutagenic and tumorigenic potential: In-vitro and in-vivo studies did not reveal any signs of any mutagenic effects of the combination of amoxicillin and clavulanic acid.
d) Reproductive toxicity: After treatment of various infections in pregnant women (approximately 560 pregnancies) with Curam Solutab no increased occurrence of malformations was observed. Amoxicillin and clavulanic acid diffuse through the placenta and are excreted into breast.

Treatment of bacterial infections induced by Gram-negative and Gram-positive amoxicillin-resistant microorganisms whose resistance is caused by β-lactamases which however are sensitive to the combination of amoxicillin and clavulanic acid.
Curam 156.25 mg/5 ml, Curam forte 312.5 mg/5 ml, Curam 375 mg, Curam 625 mg and Curam 1000 mg, Curam 457 mg/5 ml and Curam Solutab 1000 mg are suitable for treatment of the following indications when known or likely to be due to susceptible organisms (see PHARMACOLOGY: Pharmacodynamics under Actions): Infections of the upper respiratory tract (including ear-nose-throat) e.g. sinusitis, otitis media, tonsillitis.
Infections of the lower respiratory tract e.g. acute exacerbations of chronic bronchitis, bronchopneumonia, pneumonia; lung abscess (Curam FC tab/oral susp).
Genito-urinary tract infections e.g. cystitis, urethritis, pyelonephritis; pelvic infection/sepsis, gonorrhea, septic abortion (Curam FC tab/oral susp); puerperal sepsis (Curam Solutab).
Infections of the skin and soft tissues e.g. cellulitis; boils, abscesses, wound infections (Curam FC tab/oral susp and Curam Solutab); animal bites (Curam 457 mg/5 mL oral susp).
Infections of bone and joint e.g. osteomyelitis.
Dental infections e.g. dentoalveolar abscess.
Curam FC tab/oral susp: Other infections: septicaemia, peritonitis, postoperative infections.
Curam 457 mg/5 mL oral susp: Odontogenic infections (infection in the mouth, teeth).
Abdominal infections.
Curam Solutab: Intra-abdominal sepsis.

Curam FC tab/oral susp: Curam oral dosage recommendations for children below the age of 12 years are based on 25-50 mg/kg body weight/day [based on amoxicillin component], depending-on the severity of infection.
Dosage in adults and children over 12 years of age and weight over 40 kg: Mild - Moderate infections: One Curam 375 mg three times a day or every 8 hours or One Curam 625 mg two times a day or every 12 hours.
Severe infections: One Curam 625 mg three times a day or every 8 hours.
Where the 625 mg tablet is not available, a dose of two Curam 375 mg three times a day may be taken or One Curam 1000 mg two times a day or every 12 hours.
Curam 375 mg, 625 mg and 1000 mg are not recommended in children under 12 years of age and weight less than 40 kg.
Dosage in children 7-12 years: 10ml Curam 156.25 mg/5 ml suspension three times a day, or 5ml Curam forte 312.5 mg/5 ml suspension three times a day*.
Dosage in children 2-7 years: 5ml Curam 156.25 mg/5 ml suspension three times a day*.
Dosage in children 9 months-2 years: 2.5 ml Curam 156.25 mg/5 ml suspension three times a day*.
Dosage in children 0-9 months: no suitable oral presentation is currently available for this age group.
Treatment with Curam should not be extended beyond 14 days without review.
*these dosages may be doubled in severe infections.
Curam 457 mg/5 mL oral susp: The exact dose for children above 2 months of age should be based on their body weight. Depending upon severity of infection, the daily dose in children less than 40 kg body weight is 25-45 mg/kg body weight (based on the amoxicillin component), divided into two equal doses.
The measuring device is enclosed for the dosage and administration of suspension: 1 full measuring device provides 5ml, ³/₄ measuring device provides 3.75 ml, ¹/₂ measuring device provides 2.5 ml, ¹/₄ provides 1.25 ml of oral suspension.
The usual recommended daily dosage is: 25 mg/kg/day (based on the amoxicillin component) in mild to moderate infections (upper respiratory tract infections e.g. recurrent tonsillitis, lower respiratory infections and skin and soft tissue infections).
45 mg/kg/day (based on the amoxicillin component) for the treatment of more serious infections (upper respiratory tract infections e.g. otitis media and sinusitis, lower respiratory tract infections e.g. bronchopneumonia and urinary tract infections).
The tables as follows give guidance for children.
Children over 2 years: See Table 4.

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Children aged 2 months to 2 years: Children under 2 years should be dosed according to body weight. (See Table 5.)

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There is insufficient experience with Curam suspension 457 mg/5ml to make dosage recommendations for children under 2 months old.
Shake the bottle well before each using.
Curam Solutab: Dosage in adults and children over 12 years of age: The tablets should be stirred in half a glass of water (minimum 30 ml), and mixed thoroughly before taking; or placed in the mouth to disperse, before being swallowed.
Dose should be taken at regular intervals throughout the day, ideally at 8 hour intervals for Curam Solutab 625 mg and 12 hour intervals for 1 g or as prescribed.
Dosage in renal impairment/insufficiency: With renal impairment the dose should be reduced in accordance with the severity of the dysfunction and the patient's weight (Curam FC tab/oral susp and Curam Solutab).
Curam FC tab/oral susp: Adults: No change in dosage for patients with mild renal insufficiency (creatinine clearance more than 30 ml/min).
In patients with moderate renal insufficiency (creatinine clearance 10 to 30 ml/min) the dose is 1 tablet 375 mg or 1 tablet 625 mg two times a day or every 12 hours.
In patients with severe renal insufficiency (creatinine clearance less than 10 ml/min) the dose is not more than 1 tablet 375 mg every 12 hours or not more than 1 tablet 625 mg every 24 hours.
Children: No change in dosage for patients with mild renal insufficiency (creatinine clearance more than 30 ml/min).
In patients with moderate renal insufficiency (creatinine clearance 10 to 30 ml/min) the dose is 18.75 mg/kg two times a day (maximum 625 mg two times a day).
In patients with severe renal insufficiency (creatinine clearance less than 10 ml/min) the dose is 18.75 mg/kg given as a single daily dose (maximum 625 mg).
Curam 457 mg/5 mL oral susp: For children with a GFR of > 30ml/min no adjustment in dosage is required. For children with a GFR of < 30ml/min Curam 457 mg/5 ml is not recommended.
Dosage in infants with immature kidney function: For infants with immature renal function Curam 457 mg/5 ml is not recommended.
Curam Solutab: Dose in renal impairment in relation to patient weighing 70 kg: See Table 6.

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Dosage in hepatic functional impairment: Administer with caution. The liver function should be monitored at regular intervals. The experience in the use of the product in hepatic insufficiency is not adequate in order to give dose recommendations.
Curam Solutab: Curam Solutab must not be used in patients with severe hepatic functional impairment and in patients in whom hepatic functional impairment had occurred on previous therapy with Curam Solutab. Liver function parameters should be checked at regular intervals in patients with signs of hepatic lesions and a change of therapy should be given consideration if these parameters exacerbate on treatment.
Method of administration: Amoxicillin/clavulanic acid is recommended to be taken with meals to reduce any possible gastrointestinal discomfort.
Duration of administration/therapy: Curam FC tab/oral susp: The length of treatment will be decided by the physician. Do not discontinue therapy of the patient's own accord, even if patient feels better. Normally treatment with this medicine should be continued for three to four days after recovery from the illness or disappearance of the symptoms.
Treatment should not be extended beyond 14 days without review by the physician.
As a precaution, therapy over at least 10 days is indicated in the treatment of infections with β-haemolytic streptococci in order to guard against late complications (e.g. rheumatic fever, glomerulonephritis).
Curam 457 mg/5 mL oral susp: Curam 457mg/5ml should be administered for a further 3 to 4 days after improvement/regression of the symptoms and should be continued, however, for a least the generally recommended minimum period of treatment. Treatment should not be extended beyond 14 days without review by the physician.
As a precaution, over at least 10 days is indicated in the treatment of infections with beta-haemolytic streptococci in order to guard against late complications (e.g. rheumatic fever, glomerulonephritis).
If the medicinal product is forgotten to be given, give the forgotten dose as soon as remembered. But do not give the next dose too soon, it must be at minimum 4 hours between two doses. Try to carry on as before (after 12 hours give the next dose). Do not double the dose.
Curam Solutab: The duration of therapy should be determined by the response of the patient. Some infections (e.g. osteomyelitis) require longer periods of treatment. Treatment should not be extended beyond 14 days without review by the physician.

Symptoms and signs of overdose: Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see Precautions).
Convulsions may occur in patients with impaired renal function or in those receiving high doses.
Amoxicillin has been reported to precipitate in bladder catheters, predominantly after intravenous administration of large doses. A regular check of patency should be maintained (see Precautions).
Treatment of intoxication: Gastrointestinal symptoms may be treated symptomatically, with attention to the water/electrolyte balance.
Amoxicillin/clavulanic acid can be removed from the circulation by haemodialysis.

Curam FC tab/oral susp: Hypersensitivity to the active substances, to any of the penicillins or to any of the excipients.
History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam agent (e.g. a cephalosporin, carbapenem or monobactam).
History of jaundice/hepatic impairment due to amoxicillin/clavulanic acid (see Adverse Reactions).
Curam Solutab: Curam Solutab is contraindicated in patients with a previous history of hypersensitivity to amoxicillin, clavulanic acid or any of the excipients.
Curam Solutab must not be administered to patients with verified hypersensitivity to any beta-lactam drug (e.g. penicillins, cephalosporin, carbapenem, monobactam) owing to the danger of anaphylactic shock. Consequently, a careful history should be taken in regard to any allergic reactions before commencing treatment.
Curam Solutab must not be used in patients with high-grade hepatic functional impairment and in patients in whom hepatic functional impairment has occurred during previous treatment with Curam Solutab, for example cholestatic jaundice induced by Curam Solutab or penicillin.
Patients with infectious mononucleosis (glandular fever) and patients with lymphatic Leukemia have a higher risk of exanthema and consequently Curam Solutab should not be administered during these diseases to treat concomitant bacterial infections.

Before initiating therapy with amoxicillin/clavulanic acid, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam agents (see Contraindications and Adverse Reactions).
Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse reactions) have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and in atopic individuals. If an allergic reaction occurs, amoxicillin/clavulanic acid therapy must be discontinued and appropriate alternative therapy instituted.
In the case that an infection is proven to be due to an amoxicillin-susceptible organism(s) then consideration should be given to switching from amoxicillin/clavulanic acid to amoxicillin in accordance with official guidance.
This presentation of amoxicillin/clavulanic acid is not suitable for use when there is a high risk that the presumptive pathogens have reduced susceptibility or resistance to beta-lactam agents that is not mediated by beta-lactamases susceptible to inhibition by clavulanic acid. This presentation should not be used to treat penicillin-resistant S. pneumoniae.
Convulsions may occur in patients with impaired renal function or in those receiving high doses (see Adverse Reactions).
Amoxicillin/clavulanic acid should be avoided if infectious mononucleosis is suspected since the occurrence of a morbilliform rash has been associated with this condition following the use of amoxicillin.
Concomitant use of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions.
Prolonged use may occasionally result in overgrowth of non-susceptible organisms.
The occurrence at the treatment initiation of a feverish generalised erythema associated with pustula may be a symptom of acute generalised exanthemous pustulosis (AGEP) (see Adverse Reactions). This reaction requires amoxicillin/clavulanic acid discontinuation and contraindicates any subsequent administration of amoxicillin.
Amoxicillin/clavulanic acid should be used with caution in patients with evidence of hepatic impairment (see Dosage & Administration, Contraindications and Adverse Reactions).
Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged treatment. These events have been very rarely reported in children. In all populations, signs and symptoms usually occur during or shortly after treatment but in some cases may not become apparent until several weeks after treatment has ceased. These are usually reversible. Hepatic events may be severe and, in extremely rare circumstances, deaths have been reported. These have almost always occurred in patients with serious underlying disease or taking concomitant medications known to have the potential for hepatic effects (see Adverse Reactions).
Antibiotic-associated colitis has been reported with nearly all antibacterial agents including amoxicillin and may range in severity from mild to life threatening (see Adverse Reactions).
Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of any antibiotics. Should antibiotic-associated colitis occur, amoxicillin/clavulanic acid should immediately be discontinued, a physician be consulted and an appropriate therapy initiated. Anti-peristaltic medicinal products are contraindicated in this situation.
Periodic assessment of organ system functions including renal, hepatic and haematopoietic function is advisable during prolonged therapy.
Prolongation of prothrombin time has been reported rarely in patients receiving amoxicillin/clavulanic acid. Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation (see Interactions and Adverse Reactions).
In patients with renal impairment, the dose should be adjusted according to the degree of impairment (see Dosage & Administration).
In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral therapy. During the administration of high doses of amoxicillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxicillin crystalluria. In patients with bladder catheters, a regular check of patency should be maintained (see Overdosage).
During treatment with amoxicillin, enzymatic glucose oxidase methods should be used whenever testing for the presence of glucose in urine because false positive results may occur with non-enzymatic methods.
The presence of clavulanic acid in amoxicillin/clavulanic acid may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false positive Coombs test.
There have been reports of positive test results using the Bio-Rad Laboratories Platelia Aspergillus EIA test in patients receiving amoxicillin/clavulanic acid who were subsequently found to be free of Aspergillus infection. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses with Bio-Rad Laboratories Platelia Aspergillus EIA test have been reported. Therefore, positive test results in patients receiving amoxicillin/clavulanic acid should be interpreted cautiously and confirmed by other diagnostic methods.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed. However, undesirable effects may occur (e.g. allergic reactions, dizziness, convulsions), which may influence the ability to drive and use machines (see Adverse Reactions).

Pregnancy: Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see PHARMACOLOGY: Toxicology: Preclinical safety data under Actions). Limited data on the use of amoxicillin/clavulanic acid during pregnancy in humans do not indicate an increased risk of congenital malformations. In a single study in women with preterm, premature rupture of the foetal membrane it was reported that prophylactic treatment with amoxicillin/clavulanic acid may be associated with an increased risk of necrotising enterocolitis in neonates. Use should be avoided during pregnancy, unless considered essential by the physician.
Breast-feeding: Both substances are excreted into breast milk (nothing is known of the effects of clavulanic acid on the breast-fed infant). Consequently, diarrhoea and fungus infection of the mucous membranes are possible in the breast-fed infant, so that breast-feeding might have to be discontinued. The possibility of sensitisation should be taken into account.
Amoxicillin/clavulanic acid should only be used during breast-feeding after benefit/risk assessment by the physician in charge.

The most commonly reported adverse drug reactions (ADRs) are diarrhoea, nausea and vomiting.
The ADRs derived from clinical studies and post-marketing surveillance with amoxicillin/clavulanic acid, sorted by MedDRA System Organ Class are listed as follows.
The following terminologies have been used in order to classify the occurrence of undesirable effects: Very common (≥ 1/10); Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1,000 to < 1/100); Rare (≥ 1/10,000 to < 1/1,000); Very rare (< 1/10,000); Not known (cannot be estimated from the available data). (See Table 7.)

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Oral anticoagulants: Oral anticoagulants and penicillin antibiotics have been widely used in practice without reports of interaction. However, in the literature there are cases of increased international normalised ratio in patients maintained on acenocoumarol or warfarin and prescribed a course of amoxicillin. If co-administration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of amoxicillin. Moreover, adjustments in the dose of oral anticoagulants may be necessary (see Precautions and Adverse Reactions).
Methotrexate: Penicillins may reduce the excretion of methotrexate causing a potential increase in toxicity.
Probenecid: Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin. Concomitant use of probenecid may result in increased and prolonged blood levels of amoxicillin but not of clavulanic acid.
Mycophenolate mofetil: In patients receiving mycophenolate mofetil, reduction in pre-dose concentration of the active metabolite mycophenolic acid (MPA) of approximately 50% has been reported following commencement of oral amoxicillin plus clavulanic acid. The change in pre-dose level may not accurately represent changes in overall MPA exposure. Therefore, a change in the dose of mycophenolate mofetil should not normally be necessary in the absence of clinical evidence of graft dysfunction. However, close clinical monitoring should be performed during the combination and shortly after antibiotic treatment.

Incompatibilities: Not applicable.
Special precautions for disposal and other handling: Curam FC tab/oral susp: Curam 375 mg, 625 mg, 1000 mg film coated tablets: None.
Curam 156.25 mg/5 ml and 312.5 mg/5 ml powder for oral suspension: Check cap seal is intact before using.
Shake the bottle to loosen the powder. This medicinal product should not be used if lumps of powder are visible in the bottle before reconstitution.
After opening of the screw cap, check whether the sealing membrane is tightly attached to the bottle rim. In case of any signs of leakage (e.g. powder outside the bottle), do not use this bottle.
Add the prescribed quantity of water in two portions (or add to the mark) and shake well each time. (See Table 8.)

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After reconstitution the ready-for-use suspension is off-white. Do not use the reconstituted suspension if the colour is not off-white.
Curam 457 mg/5 mL oral susp: Check cap seal is intact before using.
Shake the bottle to loosen the powder, add the prescribed quantity of water in two portions (or add to the mark) and shake well each time. (See Table 9.)

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Curam Solutab: No special precautions.

Curam FC tab/oral susp and Curam Solutab: Keep in the original container. Protect from light and moisture.
Curam 457 mg/5 mL oral susp: Store the powder for oral suspension below 25°C, protect from moisture.
Keep the bottle tightly closed.
Shelf-life: Curam oral susp: The reconstituted suspension of Curam 156.25 mg/5 ml powder for oral suspension, Curam forte 312.5 mg/5 ml powder for oral suspension and Curam 457 mg/5 ml powder for oral suspension are stable for 7 days when stored at 2 - 8°C.

Penicillins

J01CR02 - amoxicillin and beta-lactamase inhibitor ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.

FC tab/Susp/Solutab: D; Inj: S